101. Sodium channel Nax is a regulator in epithelial sodium homeostasis
- Author
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Thomas A. Mustoe, Kai P. Leung, D. James Surmeier, Wei Xu, Aimei Zhong, Robert D. Galiano, Solmaz Niknam-Bienia, Shengxian Jia, D. Marshall Porterfield, Ping Xie, Michael Zeitchek, Jingling Zhao, Seok Jong Hong, and Zhong Xie
- Subjects
Epithelial sodium channel ,Keratinocytes ,medicine.medical_specialty ,Sodium ,chemistry.chemical_element ,Inflammation ,Dermatitis, Atopic ,Cicatrix ,Xenopus laevis ,Downregulation and upregulation ,Internal medicine ,medicine ,Extracellular ,Animals ,Homeostasis ,Humans ,Epithelial Sodium Channels ,Mice, Hairless ,Sodium channel ,Serine Endopeptidases ,General Medicine ,Epithelium ,Cell biology ,Up-Regulation ,Endocrinology ,medicine.anatomical_structure ,Editorial ,chemistry ,Rabbits ,medicine.symptom ,Ion Channel Gating - Abstract
The mechanisms by which the epidermis responds to disturbances in barrier function and restores homeostasis are unknown. With a perturbation of the epidermal barrier, water is lost, resulting in an increase in extracellular sodium concentration. We demonstrate that the sodium channel Nax functions as a sodium sensor. With increased extracellular sodium, Nax up-regulates prostasin, which results in activation of the sodium channel ENaC, resulting in increased sodium flux and increased downstream mRNA synthesis of inflammatory mediators. Nax is present in multiple epithelial tissues, and up-regulation of its downstream genes is found in hypertrophic scars. In animal models, blocking Nax expression results in improvement in scarring and atopic dermatitis-like symptoms, both of which are pathological conditions characterized by perturbations in barrier function. These findings support an important role for Nax in maintaining epithelial homeostasis.
- Published
- 2015